Our continuing investigative goals are to define the mechanisms of sudden death to determine predisposing "risk factors", to develop methodologic approaches for identification of subjects at risk and thereby test efficacy and safety of long term prophylactic programs. Our underlying hypothesis is that functional "risk factors" predispose to a state of myocardial electrical instability which antedates and triggers ventricular fibrillation (VF), the primary pathway to sudden death in patients with ischemic heart disease (IHD). The work will consist of the following areas of study: 1) Electrical instability - to study the preconditions (ischemia, altered neural tone, disturbed electrolyte and humoral factors) for VF during sequential R/T pulsing, to correlate these responses to single pulse-induced repetitive ventricular responses (RVR), to utilize post-overdrive pause as an assessment of automaticity and to correlate these changes with RVR and R/T pulsing. To further define the prefibrillatory state and onset mechanism of VF by adapting electrophysiologic mapping techniques to study the relationship of ventricular activation to re-entrant activity and to substantiate the electrophysiologic basis for a Type A change in monophasic action potentials as a distinctive marker for VF. 2) Protective Zone (PZ) - to define the role of the conducting system in determining the properties of this zone, to expand our studies on the PZ in relationship to ischemia and to study the effect of multiple premature beats on the PZ. 3) Nonsustained VF (NSVF) - to determine factors which favor spontaneous reversion or offset of VF and to attempt to induce NSVF in larger mammalian hearts. Exposure of patients at risk for sudden death - the presence and frequency of ventricular ectopic activity will be determined in subjects with IHD and in a normal population. Screening, 24-hour ECG ambulatory monitoring and maximal exercise testing will constitute the methods. Prophylactic measures against sudden death - to refine and elaborate methods suitable for expeditious assessment of antiarrhythmic drugs and to assess the role of exercise conditioning in control of VEA.